Efficacy and Safety in Transfusion Independent Non-severe Aplastic Anemia

Aplastic Anemia Clinical Trial

Official title:

A Randomized, Case Controlled Clinical Trial Evaluating the Efficiency and Safety of Luspatercept Plus Ciclosporin Versus Ciclosporin in Newly Diagnosed Transfusion Independent Non-severe Aplastic Anemia (NSAA).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05399732
• Other study ID #: HanB-NSAA-lus
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2022
• Est. completion date: July 2024

Study information

• Verified date: May 2022
• Source: Peking Union Medical College Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aplastic anemia (AA) is a rare bone marrow failure disease characterized by bone marrow hypocellularity and peripheral blood pancytopenia. AA is divided into severe AA (SAA) and non-severe AA (NSAA) based on the degree of cytopenia. The first line therapy for SAA or transfusion dependent NSAA is either immunosuppression therapy (IST) or hematopoietic stem cell transplantation (HSCT). Little attention has been paid to patients with anemia but not transfusion dependent, whose quality of life is significantly impaired due to the anemia and other complications.

Description:

Recombined human erythropoietin (rhEPO) has been shown to increase the erythroid response and response rate when combined with IST for patients with newly diagnosed AA, either SAA or NSAA. Different from rhEPO, luspatercept is a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands and enhances late-stage erythropoiesis, and has been shown the promising efficiency in the erythropoiesis in patients with lower risk myelodysplastic syndrome (MDS) in the phase II and III clinical trials. This randomized control study aimed to compare the 6-month efficacy and safety of the combination of luspatercept and ciclosporin versus ciclosporin monotherapy in patients with newly diagnosed transfusion independent NSAA.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: July 2024
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. age=18 year-old;

2. hemoglobin level between 60g/L~10 g/dL;

3. newly diagnosed patients have at least one of the followings: #absolute neutrophil count <1.5×109/L, #platelet count < 30×109/L, # hemoglobin level < 100g/L;

4. with normal baseline liver and kidney function;

5. with no active infection; are not pregnant or nursing;

6. agree to sign consent forms;

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

1. Congenital aplastic anemia;

2. Presence of chromosomal aberration;

3. Evidence of a clonal hematologic bone marrow disorder (MDS, AML) on cytogenetics;

4. Presence with PNH clone =50%;

5. Patients received HSCT before;

6. Uncontrolled infection or bleeding with standard treatment;

7. Allergic to luspatercept CsA or accessories;

8. HIV, HCV or HBV active infection or liver cirrhosis or portal hypertension;

9. Patient with QTcF (Fridericia's QT correction formula) at screening <450 msec, or<480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site, unstable angina pectoris, uncontrolled hypertension(>180/100mmHg)#pulmonary artery hypertension;

10. Have any concomitant malignancies within 5 years expect for local basal cell carcinoma of the skin;

11. Past history of thromboembolic event, heart attack or stroke (including anti-phospholipid antibody syndrome) and current use of anticoagulants;

12. Pregnant or nursing (lactating) woman;

13. Have attended other clinical trials within 3 months

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• Luspatercept
Patients in each group will be treated for at least 6 months and continue the treatment for an additional 6 months unless disease progress or have intolerable side effects.

Locations

Country	Name	City	State
China	Peking union medical college hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Bing Han

Country where clinical trial is conducted

China, 

References & Publications (7)

Chen WS, Zhang ML, Han B. [Evaluation of the Efficacy of Cyclosporin A Combined with Recombined Human Erythropoietin in the Treatment of Patients with Chronic Aplastic Anemia]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2021 Oct;43(5):736-742. doi: 10.3881/j.issn.1000-503X.13201. Chinese. — View Citation

Desmond R, Townsley DM, Dunbar C, Young NS. Eltrombopag in aplastic anemia. Semin Hematol. 2015 Jan;52(1):31-7. doi: 10.1053/j.seminhematol.2014.10.002. Epub 2014 Oct 31. Review. — View Citation

Drexler B, Passweg J. Current evidence and the emerging role of eltrombopag in severe aplastic anemia. Ther Adv Hematol. 2021 Mar 3;12:2040620721998126. doi: 10.1177/2040620721998126. eCollection 2021. Review. — View Citation

Furlong E, Carter T. Aplastic anaemia: Current concepts in diagnosis and management. J Paediatr Child Health. 2020 Jul;56(7):1023-1028. doi: 10.1111/jpc.14996. Epub 2020 Jul 3. Review. — View Citation

Howard SC, Naidu PE, Hu XJ, Jeng MR, Rodriguez-Galindo C, Rieman MD, Wang WC. Natural history of moderate aplastic anemia in children. Pediatr Blood Cancer. 2004 Oct;43(5):545-51. — View Citation

Matsuda K, Koya J, Arai S, Nakazaki K, Nakamura F, Kurokawa M. Cyclosporine Therapy in Patients with Transfusion-independent Non-severe Aplastic Anemia: A Retrospective Analysis. Intern Med. 2019 Feb 1;58(3):355-360. doi: 10.2169/internalmedicine.1372-18. Epub 2018 Aug 24. — View Citation

Zhang ML, Chen WS, Han B. [Evaluation of the efficacy of cyclosporin A combined with recombined human thrombopoietin for treating patients with non-severe aplastic anemia]. Zhonghua Xue Ye Xue Za Zhi. 2020 Aug 14;41(8):637-642. doi: 10.3760/cma.j.issn.0253-2727.2020.08.004. Chinese. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate (ORR)	Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR); HR defined as a hemoglobin increase from baseline of =1.5 g/dL for =2 weeks (in the absence of RBC transfusions)	6 month
Secondary	Hematologic response-erythroid(HR-E)	HR is defined as a hemoglobin increase from baseline of =1.5 g/dL for =2 weeks (in the absence of RBC transfusions	6 month
Secondary	side effects	Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.	1 year
Secondary	predictive factors	Predictors analyses will evaluate the relationship between the effect of these two treatments with molecular mutations PIGA and BCOR and BCORL1 and EPO level.	6 month